Microorganisms cause disease if they overcome host defenses or if the host defenses are impaired. The ability of the host to ward off disease through natural defenses either specific or nonspecific (Table 1.1), is known as resistance and the lack of resistance is known as vulnerability.
The term ‘opportunistic infection’ is applied to an infection occurring in an immunocompromised host with impaired defense mechanisms.
“Immunocompromised host” describes a group of individuals with impairment of either natural or specific immunity or both so that they are at an increased risk of contracting infection by a variety of microorganisms. Host defense mechanisms could be impaired by various etiological factors (Table 1.2). Defects in host defense mechanisms may lead to emergence of various opportunistic infections.
The microorganisms that invade the individuals may be grouped into three major categories.
- True pathogens: Involve the normal and abnormal host alike, e.g. Haemophilus influenzae Salmonella typhi
- Sometimes pathogens: They are commonly present as colonizers of the muco-cutaneous surface. They cause clinical disease only when introduced into normally sterile tissues following a break in the integrity of a mucocutaneous surface, e.g.staphylococcal and group A streptococcal sepsis following break in skin integrity and gram-negative and Bacteroides fragilis sepsis following bowel perforation.2
Table 1.2 Causes of impaired host defenses ImmunodeficiencyOrgan damage/ dysfunctionDepletion of competing endogenous floraInborn: CGD, SCID, MPD, HypogammaglobulinemiaSkin: Surgery, IV catheters and devices, Eczema, BurnsBroad spectrum antibioticsDrug induced: Chemotherapy, Radiotherapy, Corticosteroids, Other immunosuppressive agentsMucosa: Ulcers, Suppressed mucociliary actionAcquired: AIDS, Solid and Hematologic malignancies, Malnutrition, Diabetes with Ketoacidosis, CMV infection AgranulocytopeniaSystemic disorders: Diabetes Mellitus, Renal failure, Liver failure, COPD/Lung dysfunction, Splenectomy, Sickle cell anemiaAge related: Neonates, ElderlyAbbreviations: CGD – Chronic granulomatous disease, SCID – Severe combined immunodeficiency MPD – Myeloperoxidase deficiency, IV – Intravenous, COPD – Chronic obstructive pulmonary disease - Nonpathogens: They usually have no impact on the normal host, being capable of invading and causing disease only in individuals with impairment of either nonspecific or specific host defenses or both.
Stricter definition of ‘opportunistic infection’ limits the term either to infections caused by organisms not normally recognized as pathogens (nonpathogens) but which invade the body because of specific immunodeficiencies, or to infections by known pathogens (true/ sometimes pathogens) occurring at unusual sites to which they gain access as a result of physical or immunological breaches in host defenses, or of a severity rarely encountered in the normal host (e.g. disseminated zoster in the lymphoma patients, recurrent salmonellosis in AIDS patients). The increasing interest in the immunocompromised host and opportunistic infections is a reflection of two important events; the first is the advent of the AIDS epidemic, and the second is because of major advances in transplantation, cancer chemotherapy and the treatment of a variety of autoimmune conditions. The dramatic increase in the diversity and number of opportunistic infections is not only due to an increasing population of susceptible individuals but also due to an improved recognition by advanced laboratory diagnostic techniques.
Infections in transplant patients arise most commonly as a result of invasion by endogenous opportunists following immunosuppressive therapy with drugs such as corticosteroids, cyclosporine and azathioprine. It may also follow colonization by exogenous 3environmental organisms and via transfer of cytomegalovirus along with the transplanted kidney. The overall incidence of opportunistic infections varies from one center to another; up to 15 percent renal transplant recipients die of these infections.
The list of agents causing opportunistic infections is exhaustive; however, some of the commonly encountered agents are outlined in Table 1.3. The bacteria are prokaryotes where as fungi and parasites are eukaryotes. Viruses fall into neither category and rely on the biochemical processes of the host cell for their replication and propagation.
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GENERAL APPROACH TO MANAGEMENT
There are a number of essential principles in the management of opportunistic infections.
- Recognition of infection: Clinical signs and symptoms of infection in immunocompromised patients may be less overt than in normal individuals and may commonly be concealed or imitated by the underlying disease. A high index of clinical suspicion is vital. The unusual pathogens encountered in these patients demand thorough investigations.
- Identification of the site of infection: This assists in differential diagnosis, e.g. pneumonitis in transplant patients may commonly be due to CMV or Pneumocystis carinii infection. Clinical examination should also include areas such as the perineum and oropharynx.
- Assessment of urgency of empirical therapy: In some patients there may be sufficient time for adequate investigations and specific chemotherapy. In others, the potential for rapid mortality necessitates urgent empirical ‘best guess’ therapy.
- Choice of chemotherapy and assessment of efficacy: Response to routine monotherapy may be suboptimal in immunocompromised patients and combination chemotherapy is often required from the outset.